[Waardenburg syndrome. A heterogenic disorder with variable penetrance]. / Waardenburg-Syndrom. Eine heterogene Erkrankung mit variabler Penetranz.

BACKGROUND: Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. PATIENTS AND METHODS: Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. RESULTS AND CONCLUSION: In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.

A metal ring that had been lodged in a child's nasopharynx for 4 years.

A considerable number of articles on foreign-body ingestion and inhalation have been reported in the literature. Of these, nasopharyngeal foreign bodies are rare. Unless they cause total obstruction, symptoms typically appear late. Foreign bodies, especially metal ones, can lodge in soft tissue, and their removal can be rather complicated. In this article, we describe the case of a 4-year-old girl who had had a gold ring lodged in her nasopharynx. The history led us to determine that the ring had been there since the child was 3 months old. A flexible fiberoptic nasopharyngeal examination revealed that the ring was embedded in the nasal surface of the soft palate and was enclosed by a thin layer of mucosal membrane. With the patient under general anesthesia, we were able to remove the foreign body with a 0 degree endoscope.

Transcranial Doppler detection of microembolic signals in patients with Behçet's disease.

We evaluated the prevalence of microembolic signals (MES) in patients with Behçet's disease (BD). We also attempted to determine the frequency of MES in BD patients with or without neurological involvement. This study enrolled 55 patients fulfilling the diagnostic criteria of International Study Group for BD. Bilateral transcranial Doppler ultrasound of the middle cerebral arteries was performed. MES were identified based on the criteria of International Consensus group on Microembolus Detection. Patients with BD were divided into two groups in respect of the presence of neurological involvement (n = 10) or not (n = 45), and counts of MES in the two were compared with each other and with normal subjects. We found MES in 16 patients (29%) with BD. The frequency was higher in patients with neurological involvement than in those without (80% vs. 17%, P< 0.001). In patients with neurological involvement there was a positive correlation in regression analysis between the prevalence of MES and disease duration (P = 0.025). There was a significantly higher prevalence of MES in BD patients than in control subjects. The frequency of MES was higher in patients with neurological involvement than in those without. TCD detection of MES may allow the recognition of subset of patients at high risk for the appearance of neurological involvement.

Clinical evidence for dystrophin dysfunction as a cause of hearing loss in locus DFN4.

OBJECTIVE: Locus DFN4 is an X-linked nonsyndromic hearing loss locus originally mapped to Xp21.2. Recently, we have mapped deafness in a second family from Turkey to the same region, refining the location to within the Duchenne muscular dystrophy (DMD) locus. The objective of this study was to characterize the clinical phenotype of the Turkish family with comprehensive audiovestibular testing and high-resolution temporal bone computerized tomography. METHODS: Fourteen members of a three-generation family were studied in detail including two deaf affected males. Members of the family underwent general physical and otologic examination, vestibular testing, pure-tone audiometry, otoacoustic emissions, and immitance testing. An affected male underwent high-resolution computerized tomography of the temporal bone, electroretinogram (ERG), electromyography, electroneurography, and determination of serum creatinine phosphokinase level. RESULTS: Affected males were congenitally deaf with normal vestibular function. Carrier females showed a mild sensorineural hearing loss affecting all frequencies and absent otoacoustic emissions. Otoacoustic emissions in a younger, 3-year-old carrier girl were normal. In an affected male, ERG demonstrated subnormal scotopic b-wave typically seen in DMD. Computerized tomography of the temporal bone was normal. With the exception of the ERG finding, there was no clinical or laboratory evidence of DMD or Becker muscular dystrophy (BMD). CONCLUSION: The abnormal ERG in the Turkish family in conjunction with mapping of the DFN4 locus to within DMD strongly suggests that a defect in dystrophin is responsible for the hearing loss in this family. Patients with DMD and BMD should be screened systematically for sensorineural hearing loss. This family provides additional evidence for the critical role of cytoskeletal proteins in normal hearing.

A second family with nonsyndromic sensorineural hearing loss linked to Xp21.2: refinement of the DFN4 locus within DMD.

X-linked inherited hearing impairment is a group of heterogeneous disorders accounting for less than 2% of hereditary hearing loss. DFN4, a sex-linked hearing impairment associated with profound sensorineural hearing loss, has been previously mapped to Xp21.2, a region containing the DMD locus. We have identified a family from Turkey with deafness in which the disease maps to and refines the DFN4 locus. In contrast to the previous family, the crossover points are entirely within the DMD locus. Two-point lod score analysis for the markers DXS 997, DXS 1214, and DXS 1219 showed a lod score of 2. 59. 5' and 3' crossovers were between DMD 44 and DXS 1219 and between DXS 1214 and DXS 985, respectively, suggesting that DFN4 is either an allele of DMD or a mutation in a DMD nested gene. The restriction of the DFN4 locus to DMD suggests that dystrophin may play an important role in hearing.